Ionic liquid-promoted, highly regioselective Heck arylation of electron-rich olefins by aryl halides

Article abstract of DOI:10.1021/ja0450861

Palladium-catalyzed regioselective Heck arylation of the electron-rich olefins, vinyl ethers 1a-d, enamides 1e-g, and allyltrimethylsilane 1h, has been accomplished in imidazolium ionic liquids with a wide range of aryl bromides and iodides instead of the commonly used, but commercially unavailable and expensive, aryl triflates. The reaction proceeded with high efficiency and remarkable regioselectivity without the need for costly or toxic halide scavengers, leading exclusively to substitution by aryl groups of diverse electronic and steric properties at the olefinic carbon α to the heteroatom of 1a-g and β to the heteroatom of 1h. In contrast, the arylation reaction in molecular solvents led to mixtures of regioisomers under similar conditions. Several lines of evidence point to the unique regiocontrol stemming from the ionic environment provided by the ionic liquid that alters the reaction pathway. The chemistry provides a simple, effective method for preparing branched, arylated olefins and contributes to the extension of Heck reaction to a wider range of substrates.

Full text of DOI:10.1021/ja0450861

Published on Web 12/16/2004
Ionic Liquid-Promoted, Highly Regioselective Heck Arylation
of Electron-Rich Olefins by Aryl Halides
Jun Mo, Lijin Xu, and Jianliang Xiao*
Contribution from the Department of Chemistry, LiVerpool Centre for Materials and Catalysis,
UniVersity of LiVerpool, LiVerpool L69 7ZD, U.K.
Received August 16, 2004; E-mail: j.xiao@liv.ac.uk
Abstract: Palladium-catalyzed regioselective Heck arylation of the electron-rich olefins, vinyl ethers 1a-
d, enamides 1e-g, and allyltrimethylsilane 1h, has been accomplished in imidazolium ionic liquids with a
wide range of aryl bromides and iodides instead of the commonly used, but commercially unavailable and
expensive, aryl triflates. The reaction proceeded with high efficiency and remarkable regioselectivity without
the need for costly or toxic halide scavengers, leading exclusively to substitution by aryl groups of diverse
electronic and steric properties at the olefinic carbon R to the heteroatom of 1a-g and â to the heteroatom
of 1h. In contrast, the arylation reaction in molecular solvents led to mixtures of regioisomers under similar
conditions. Several lines of evidence point to the unique regiocontrol stemming from the ionic environment
provided by the ionic liquid that alters the reaction pathway. The chemistry provides a simple, effective
method for preparing branched, arylated olefins and contributes to the extension of Heck reaction to a
wider range of substrates.
Introduction
and a similar reaction involving 4-dimethylaminobromobenzene
catalyzed by Fu’s versatile Pd-P(t-Bu)3 catalyst led to an R/â
Palladium-catalyzed arylation or vinylation of olefins by aryl
or vinyl halides, that is, the Heck reaction, has become one of
the most useful tools for constructing C-C bonds in synthetic
chemistry.1,2 Thus far, most of the reported Heck reactions deal
with olefins bearing electron-withdrawing substituents, such as
-CO2R and -CN, which selectively lead to products resulting
from arylation or vinylation at the less-substituted (â) position
of the olefin double bond. With electron-rich olefins, such as
acyclic enol ethers, silanes, and enol amides, an important issue
arises; the reaction is rarely regioselective under normal Heck
conditions, giving rise to a mixture of R- and â-substituted
olefins and thus hampering its wider application in synthesis
(eq 1).1a,c,d,h,3-6 For instance, arylation of butyl vinyl ether with
4-bromoanisole catalyzed by the well-known Herrmann-Beller
palladacycle yielded two olefins, with an R/â ratio of 10/13,4m
ratio of 4/1.4h Poor regioselectivity alongside poor yield has also
been observed with some of the most active heterogeneous
palladium catalysts.4i In fact, few catalytic systems have been
developed which allow for the regioselective, intermolecular
(4) For some recent examples of regioisomer formation, see: (a) Park, S. B.;
Alper, H. Org. Lett. 2003, 5, 3209. (b) Xu, L.; Mo, J.; Baillie, C.; Xiao, J.
J. Organomet. Chem. 2003, 687, 301. (c) Calo, V.; Nacci, A.; Monopoli,
A.; Spinelli, M. Eur. J. Org. Chem. 2003, 1382. (d) Hierso, J. C.; Fihri,
A.; Amardeil, R.; Meunier, P.; Doucet, H.; Santelli, M.; Donnadieu, B.
Organometallics 2003, 22, 4490. (e) Maeda, K.; Farrington, E. J.; Galardon,
E.; John, B. D.; Brown, J. M. AdV. Synth. Catal. 2002, 344, 104. (f)
Schnyder, A.; Aemmer, T.; Indolese, A. F.; Pittelkow, U.; Studer, M. AdV.
Synth. Catal. 2002, 344, 495. (g) Feuerstein, M.; Doucet, H.; Santellic, M.
Tetrahedron Lett. 2002, 43, 2191. (h) Littke, A. F.; Fu, G. C. J. Am. Chem.
Soc. 2001, 123, 6989. (i) Djakovitch, L.; Koehler, K. J. Am. Chem. Soc.
2001, 123, 5990. (j) Bergbreiter, D. E.; Osburn, P. L.; Wilson, A.; Sink, E.
M. J. Am. Chem. Soc. 2000, 122, 9058. (k) Ludwig, M.; Stromberg, S.;
Svesson, M.; Akermark, B. Organometallics 1999, 18, 970. (l) Wright, S.
W.; Hageman, D. L.; McClure, L. D. J. Heterocycl. Chem. 1998, 35, 717.
(m) Herrmann, W. A.; Brossmer, C.; Reisinger, C. P.; Riermeier, T. H.;
O¨ fele, K.; Beller, M. Chem.sEur. J. 1997, 3, 1357.
(5) Regiocontrol is possible for coupling partners containing functionalities
capable of chelating to palladium. For examples, see: (a) Svennebring,
A.; Nilsson, P.; Larhed, M. J. Org. Chem. 2004, 69, 3345. (b) Nilsson, P.;
Larhed, M.; Hallberg, A. J. Am. Chem. Soc. 2003, 125, 3430. (c) Glorius,
F. Tetrahedron Lett. 2003, 44, 5751. (d) Barcia, J. C.; Cruces, J.; Estevez,
J. C.; Estevez, R. J.; Castedo, L. Tetrahedron Lett. 2002, 43, 5141. (e)
Cruces, J.; Estevez, J. C.; Castedo, L.; Estevez, R. J. Tetrahedron Lett.
2001, 42, 4825. (f) Crisp, G. T.; Gebauer, M. G. Tetrahedron 1996, 52,
12465. (g) Larhed, M.; Andersson, C. M.; Hallberg, A. Tetrahedron 1994,
50, 285. (h) Badone, D.; Guzzi, U. Tetrahedron Lett. 1993, 34, 3603. (i)
Larhed, M.; Andersson, C. M.; Hallberg, A. Acta Chem. Scand. 1993, 47,
212. (j) Andersson, C. M.; Larsson, J.; Hallberg, A. J. Org. Chem. 1990,
55, 5757. Aldimines and aldehydes have recently been shown to undergo
coupling with Ar-I to give products similar to the branched olefins under
question: (k) Ishiyama, T.; Hartwig, J. J. Am. Chem. Soc. 2000, 122, 12043.
(l) Huang, Y. C.; Majumdar, K. K.; Cheng, C. H. J. Org. Chem. 2002, 67,
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(1) For recent reviews, see: (a) Larhed, M.; Hallberg, A. In Handbook of
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I. P.; Cheprakov, A. V. Chem. ReV. 2000, 100, 3009. (d) Hegedus, L. S.
Transition Metals in the Synthesis of Complex Organic Molecules, 2nd
ed.; University Science Books: Sausalito, CA, 1999; Chapter 4.6. (e) Brase,
S.; de Meijere, A. In Metal-Catalyzed Cross-coupling Reactions; Diederich,
F., Stang, P. J., Eds.; Wiley-VCH: Weinheim, Germany, 1998; Chapter 3.
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19, 101. (b) de Vries, J. G. Can. J. Chem. 2001, 79, 1086. (c) Eisenstadt,
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1998; p 576.
(6) Regiocontrol is also possible with intramolecular coupling of iodides, where
intramolecular coordination of the olefin may facilitate dissociation of the
iodide anion to form the cationic palladium intermediate (Scheme 1):
Ashimori, A.; Bachand, B.; Calter, M. A.; Govek, S. P.; Overman, L. E.;
Poon, D. J. J. Am. Chem. Soc. 1998, 120, 6488.
(3) Cabri, W.; Candiani, I. Acc. Chem. Res. 1995, 28, 2. (b) Davis, G. D., Jr.;
Hallberg, A. Chem. ReV. 1989, 89, 1433.
9
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J. AM. CHEM. SOC. 2005, 127, 751-760
751

A R T I C L E S
Scheme 1
Mo et al.
arylation of such electron-rich olefins by using the aryl halides
ArX (X ) I, Br, or Cl) without special additives.
incentive to develop cleaner catalytic systems that tolerate aryl
halides and obviate the need for copious quantities of inorganic
additives.
The results obtained by Cabri and others with electron-rich
olefins can be rationalized by the simplified mechanism
illustrated in Scheme 1.1,6,9,12,13 The key aspect of the mechanism
is that the reaction may proceed via two pathways, a neutral
pathway A that leads mainly to the formation of a linear or
â-substituted olefin and an ionic pathway B that yields
predominately a branched or R-product.9,12,13a-c Pathway A is
The regioselectivity of the Heck reaction has been a topic of
research for many years.1a,c,d,h,3,7 Earlier studies by Hallberg and
co-workers show that the regiocontrol in arylation of enol ethers
is governed by a range of parameters, including, among others,
the electronic properties of the aromatic rings and the choice
of ligands and halide additives.3b,5g,i,j,8 A significant advance
was made by Cabri and co-workers, who found that the
regioselectivity of arylation of electron-rich olefins could be
controlled by the choice of ligands and the leaving groups of
aryl substrates, regardless of other variables.3a,9 Thus, in the
particular case of acyclic enol ethers, such as butyl vinyl ether,
regioselectivities of >99/1, as measured by the R/â ratios, and
markedly improved rates were attained in DMF when bidentate
ligands were employed for palladium and when the arylating
halides were replaced by triflates or when a stoichiometric
quantity of silver or thallium salt was added in the case of aryl
halides as the arylating agents.9a-c This approach has consider-
ably extended the scope of the Heck reaction and has since been
exploited in a number of synthetic reactions, including, in
(10) For examples from Hallberg and co-workers, see: (a) Vallin, K. S. A.;
Zhang, Q.; Larhed, M.; Curran, D. P.; Hallberg, A. J. Org. Chem. 2003,
68, 6639. (b) Bengtson, A.; Larhed, M.; Hallberg, A. J. Org. Chem. 2002,
67, 5854. (c) Olofsson, K.; Sahlin, H.; Larhed, M.; Hallberg, A. J. Org.
Chem. 2001, 66, 544. (d) Nilsson, P.; Larhed, M.; Hallberg, A. J. Am.
Chem. Soc. 2001, 123, 8217. (e) Vallin, K. S. A.; Larhed, M.; Johansson,
K.; Hallberg, A. J. Org. Chem. 2000, 65, 4537. (f) Olofsson, K.; Larhed,
M.; Hallberg, A. J. Org. Chem. 2000, 65, 7235. (g) Olofsson, K.; Larhed,
M.; Hallberg, A. J. Org. Chem. 1998, 63, 5076. (h) Larhed, M.; Hallberg,
A. J. Org. Chem. 1996, 61, 9582.
(11) For recent examples, see: (a) Tu, T.; Hou, X. L.; Dai, L. X. Org. Lett.
2003, 5, 3651. (b) Legros, J.-Y.; Primault, G.; Fiaud, J.-C. Tetrahedron
2001, 57, 2507. (c) Sakagami, H.; Ogasawara, K. Heterocycles 2001, 54,
43. (d) Wu, J.; Marcoux, J. F.; Davies, I. W.; Reider, P. J. Tetrahedron
Lett. 2001, 42, 159. (e) Wegge, T.; Schwarz, S.; Seitz, G. Tetrahedron:
Asymmetry 2000, 11, 1405. (f) Homan, E. J.; Tulp, M. Th. M.; Nilsson, J.
E.; Wikstrom, H. V.; Grol, C. J. Bioorg. Med. Chem. 1999, 7, 2541. (g)
Savelon, L.; Bizot-Espiard, J. G.; Caignard, D. H.; Pfeiffer, B.; Renard,
P.; Viaud, M. C.; Guillaumet, G. Bioorg. Med. Chem. 1998, 6, 1963. (h)
Subramanyam, C.; Chattarjee, S.; Mallamo, J. P. Tetrahedron Lett. 1996,
37, 459. (i) Pendrak, I.; Chambers, P. A. J. Org. Chem. 1995, 60, 3249. (j)
Liljebris, C.; Selen, G.; Resul, B.; Stjernschantz, J.; Hacksell, U. J. Med.
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(12) Ozawa, F.; Kubo, A.; Hayashi, T. J. Am. Chem. Soc. 1991, 113, 1417. (b)
Sato, Y.; Sodeoka, M.; Shibasaki, M. Chem. Lett. 1990, 1953.
particular, those that lead to bioactive compounds.10,11
A
(13) For examples of mechanistic studies of the Heck reaction with bidentate
ligands, see: (a) Deeth, R. J.; Smith, A.; Brown, J. M. J. Am. Chem. Soc.
2004, 126, 7144. (b) von Schenck, H.; Akermark, B.; Svensson, M. J. Am.
Chem. Soc. 2003, 125, 3503. (c) von Schenck, H.; Akermark, B.; Svensson,
M. Organometallics 2002, 21, 2248. (d) Alcazar-Roman, L. M.; Hartwig,
J. F. Organometallics 2002, 21, 491. (e) Hii, K. K.; Claridge, T. D. W.;
Brown, J. M.; Smith, A.; Deeth, R. J. HelV. Chim. Acta 2001, 84, 3043. (f)
von Schenck, H.; Stromberg, S.; Zetterberg, K.; Ludwig, M.; Akermark,
B.; Svensson, M. Organometallics 2001, 20, 2813. (g) Sundermann, A.;
Uzan, O.; Martin, J. M. L. Chem.sEur. J. 2001, 7, 1703. (h) Casey, M.;
Lawless, J.; Shirran, C. Polyhedron 2000, 19, 517. (i) Amatore, C.; Jutand,
A. J. Organomet. Chem. 1999, 576, 254. (j) Shaw, B. L. New. J. Chem.
1998, 77. (k) Albert, K.; Gisdakis, P.; Ro¨sch, N. Organometallics 1998,
17, 1608. (l) Brown, J. M.; Hii, K. K. Angew. Chem., Int. Ed. Engl. 1996,
35, 657. (m) Refs 4k and 6. For some related studies, see: (n) Rosner, T.;
Bars, J. L.; Pfaltz, A.; Blackmond, D. G. J. Am. Chem. Soc. 2001, 123,
1848. (o) Bo¨hm, V. P. W.; Herrmann, W. A. Chem.sEur. J. 2001, 7, 4191.
(p) van Strijdonck, G. P. F.; Boele, M. D. K.; Kamer, P. C. J.; de Vries, J.
G.; van Leeuwen, P. W. N. M. Eur. J. Inorg. Chem. 1999, 1073. (q) Beller,
M.; Riermeier, T. H. Eur. J. Inorg. Chem. 1998, 29.
significant drawback of the chemistry is that triflates are base
sensitive, thermally labile, and rarely commercially available,
and when halides are used, stoichiometric, costly silver salts or
toxic thallium salts are necessary. Hence, there clearly exists
(7) Heck, R. F. Acc. Chem. Res. 1979, 12, 146. (b) Daves, G. D., Jr. Acc.
Chem. Res. 1990, 23, 201.
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Andersson, C. M.; Hallberg, A. J. Org. Chem. 1988, 53, 235. (c) Andersson,
C. M.; Hallberg, A. J. Org. Chem. 1988, 53, 2112. (d) Andersson, C. M.;
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Cabri, W.; Candiani, I.; Bedeschi, A. J. Org. Chem. 1992, 57, 3558. (c)
Cabri, W.; Candiani, I.; Bedeschi, A.; Penco, S. J. Org. Chem. 1992, 57,
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752 J. AM. CHEM. SOC. VOL. 127, NO. 2, 2005

Heck Arylation of Electron-Rich Olefins by Aryl Halides
A R T I C L E S
Scheme 2
characterized by dissociation of one of the coordinating neutral
phosphorus atoms, while pathway B generates a coordinating
site for the incoming olefin by dissociation of the halide anion.
Understandably, with monodentate phosphine ligands and aryl
halides, the neutral pathway would dominate due to easy
dissociation of the ligand and the relatively strong Pd-X bonds
formed following oxidative addition of ArX (X ) I, Br, or Cl)
to the Pd(0) species.14,15 In contrast, the liability of the Pd-
OTf bond means that the ionic route would be favored when
using aryl triflates (X ) OTf),13l,16 particularly in the presence
of a chelating bidentate ligand. Recent theoretical calculations
have shed more light on the mechanisms, showing that when
following pathway B, electron-rich olefins tend to afford the
R-arylated olefin, and this is driven primarily by electrostatic
(as a result of charge difference) and frontier orbital inter-
actions.13a-c,17 Of further interest is that both experimental and
theoretical studies have suggested that for a given olefin, it may
be possible to alter the regioselectivity by choosing the reaction
pathway.3a,13b In this context, an important observation is that
the reaction pathway can indeed be switched from neutral to
ionic and vice versa. Thus, when starting with a halide substrate,
addition of a halide-sequestrating agent, such as AgOTf or
TlOAc, alters the reaction route from A to B, and when the
substrate is a triflate, addition of halide salts generates the neutral
halide-containing species in path A.3a,5g,8c,16,18
In a program aimed at developing metal-catalyzed reactions
in ionic liquids,19 we thought that the ionic pathway might be
promoted by using ionic liquids as solvents, producing branched
olefins without calling for a halide scavenger. Ionic liquids are
entirely composed of ions; hence, electrostatic interactions would
favor the generation of a Pd-olefin cation and a halide anion
from two neutral precursors over that of a neutral Pd-olefin
intermediate from the same.20 In fact, studies by Amatore and
Jutand have shown that the neutral complex [(PPh3)2Pd(Ar)X]
is in equilibrium with [(PPh3)2Pd(Ar)(DMF)]+ and X- (X )
Cl, Br, or I) in DMF,15a,21 and an earlier study by Milstein has
revealed that olefin insertion into the Pd-Ar bond in [L2Pd-
(Ar)X] (L2 ) diphosphine) is greatly facilitated in a polar
solvent, due to stabilization of the ionic species generated by
halide dissociation.22 Additionally, with dialkylimidazolium-
based ionic liquid solvents, the acidic C2-H proton of the
imidazolium ring is well-known to hydrogen bond to halide
anions;23 so we initially thought this hydrogen bonding might
also help accelerate the ionic reaction by contributing to the
dissociation from palladium of a halide anion and its stabiliza-
tion.
Indeed, we have found that, using the ionic liquid 1-butyl-
3-methylimidazolium tetrafluoroborate ([bmim][BF4]) as sol-
vent, the Heck arylation of the electron-rich olefins 1a-h can
be accomplished in excellent regioselectivity with a wide variety
of aryl bromides and iodides with no need for aryl triflates or
halide scavengers (Scheme 2; the isolated product was ketone
5 in the case of 1a-d). In line with the reasoning above,
Hallberg and co-workers reported, shortly after our initial
report,19d that highly regioselective arylation of vinyl ethers by
aryl bromides could also be achieved in the ionic liquid 1-butyl-
3-methylimidazolium hexafluorophosphate ([bmim][PF6])24 as
well as in aqueous DMF,25 in which water acts as a polarity
promoter and is indispensable.26 However, the DMF-H2O
system was shown to be ineffective toward aryl iodides, and
only one example was reported for the reaction in [bmim][PF6].
More recently, Alper and co-workers reported the arylation of
tert-butyl vinyl ether by iodobenzene to give a 9/1 R/â
regioselectivity using a Pd-bisimidazole catalyst in [bmim]-
[PF6].4a
(14) Henry, P. M. Palladium Catalyzed Oxidation of Hydrocarbons; D. Riedel:
Dordrecht, The Netherlands, 1980; p 11.
(15) Dissociation of X- from [(PPh3)2Pd(Ar)X] (X ) Cl, Br, I, OAc) to give
[(PPh3)2Pd(Ar)(DMF)]+ took place in DMF but not in the less-polar THF:
(a) Amatore, C.; Carre, E.; Jutand, A. Acta Chem. Scand. 1998, 52, 100.
[(AsPh3)2PdPhI] does not appear to undergo any appreciable dissociation
in DMF, however: (b) Casares, J. A.; Espinet, P.; Salas, G. Chem.sEur.
J. 2002, 8, 4844.
Room temperature ionic liquids, such as those based on
imidazolium salts, have widely been recognized as one of the
most promising alternatives to hazardous organic solvents for
clean chemical reactions, due to their extremely low vapor
pressure and their novel, tunable physicochemical properties.27
A great number of catalytic reactions have proved feasible in
these ionic liquids, with many displaying enhanced reactivities
and selectivities, some of which have not been seen in common
organic solvents.28,29 Herein, we report the details of the
regioselective arylation of 1a-h by activated and deactivated
aryl bromides and iodides in [bmim][BF4] and some observa-
(16) Jutand, A.; Mosleh, A. Organometallics 1995, 14, 1810. (b) Jutand, A.
Eur. J. Inorg. Chem. 2003, 2017.
(17) Andappan, M. M. S.; Nilsson, P.; von Schenck, H.; Larhed, M. J. Org.
Chem. 2004, 69, 5212.
(18) Jutand, A.; Hii, K. K.; Thornton-Pett, M.; Brown, J. M. Organometallics
1999, 18, 5367. (b) Grigg, R.; Loganathan, V.; Santhakumar, V.; Sridharan,
V.; Teasdale, A. Tetrahedron Lett. 1991, 32, 687. (c) Larock, R. C.; Gong,
W. H.; Baker, E. Tetrahedron Lett. 1989, 30, 2603. (d) Ref 6.
(19) Ross, J.; Xiao, J. Chem.sEur. J. 2003, 9, 4900. (b) Ref 4b. (c) Ross, J.;
Xiao, J. Green Chem. 2002, 4, 129. (d) Xu, L.; Chen, W.; Ross, J.; Xiao,
J. Org. Lett. 2001, 3, 295. (e) Ross, J.; Chen, W.; Xu, L.; Xiao, J.
Organometallics 2001, 20, 138. (f) Xu, L.; Chen, W.; Xiao, J. Organo-
metallics 2000, 19, 1123. (g) Chen, W.; Xu, L.; Chatterton, C.; Xiao, J.
Chem. Commun. 1999, 1247.
(20) For references concerning the polarities of imidazolium ionic liquids, see:
(a) Thomazeau, C.; Olivier-Bourbigou, H.; Magna, L.; Luts, S.; Gilbert,
B. J. Am. Chem. Soc. 2003, 125, 5264. (b) Anderson, J. L.; Ding, J.; Welton,
T.; Armstrong, D. W. J. Am. Chem. Soc. 2002, 124, 14247. (c) Aki, S. N.;
Brennecke, J. F.; Samanta, A. Chem. Commun. 2001, 413. (d) Muldoon,
M. J.; Gordon, C. M.; Dunkin, I. R. J. Chem. Soc., Perkin Trans. 2 2001,
433. (e) Fletcherm, K. A.; Stoery, I. A.; Hendricks, A. E. Green Chem.
2001, 3, 210. (f) Carmichael, A. J.; Seddon, K. R. J. Phys. Org. Chem.
2000, 13, 591. (g) Bonhote, P.; Das, A.; Papageorgiou, N.; Kalanasundram,
K.; Graetzel, M. Inorg. Chem. 1996, 35, 1168.
(22) Portnoy, M.; Ben-David, Y.; Rousso, I.; Milstein, D. Organometallics 1994,
13, 3465.
(23) Avent, A. G.; Chaloner, P. A.; Day, M. P.; Seddon, K. R.; Welton, T. J.
Chem. Soc., Dalton Trans. 1994, 3405 and references therein. For more
recent examples, see: (b) Ko¨lle, P.; Dronskowski, R. Inorg. Chem. 2004,
43, 2803 and references cited in ref 19a.
(24) Vallin, K. S. A.; Emilsson, P.; Larhed, M.; Hallberg, A. J. Org. Chem.
2002, 67, 6243.
(25) Vallin, K. S. A.; Larhed, M.; Hallberg, A. J. Org. Chem. 2001, 66, 4340.
(26) Opposite regioselectivities have been observed when the reaction is run in
poly(ethylene glycol): Chandrasekhar, S.; Narsihmulu, Ch.; Sultana, S. S.;
Reddy, N. R. Org. Lett. 2002, 4, 4399.
(21) The equilibrium constant for (PPh3)2Pd(Ar)+ + X- h (PPh3)2Pd(Ar)X
ranges from 1.7 × 103 mol-1 dm3 for X ) I to 19 × 103 mol-1 dm3 for X
) Cl: ref 15a.
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J. AM. CHEM. SOC. VOL. 127, NO. 2, 2005 753

A R T I C L E S
Mo et al.
Table 1. Solvent Effect on the Heck Arylation of Butyl Vinyl Ether
1a by 4-Bromobenzaldehyde 2aa
tions concerning the reaction mechanism. To the best of our
knowledge, the catalytic system to be described represents the
only reported protocol, with which the intermolecular Heck
arylation of the three classes of electron-rich olefins 1a-h can
be affected with both aryl bromides and iodides in a highly
regioselective manner with no need for a halide scavenger.
Results and Discussion
Effects of Solvents. To determine if direct, regioselective
arylation of electron-rich olefins by aryl halides could occur in
ionic liquids without using any inorganic salt additives, we
examined the arylation of 1a by 4-bromobenzaldehyde 2a in
[bmim][BF4] under conditions previously optimized for triflates
using molecular solvents, where the active catalyst was derived
in situ from Pd(OAc)2 and 1.1 equiv of a diphosphine, 1,3-bis-
(diphenylphosphino)propane (DPPP).9c For comparison, the
same reaction experiment was also carried out in common
organic solvents. In a typical reaction, a mixture of 1a, 2a, Pd-
(OAc)2, and DPPP was heated in a chosen solvent for a certain
period of time under an inert atmosphere. The R-arylated product
3a was isolated, when necessary, as the aryl methyl ketone 5a
following acidification. The results are given in Table 1. Much
conv.
solvent
(%)b
R
/
âc
E/Zd
[bmim][BF4]
toluene
dioxane
acetonitrile
DMAc
100
18
26
33
98
>99/1
47/53
35/65
45/55
24/76
47/53
86/14
68/32
82/18
63/37
74/26
80/20
79/21
DMF
DMSO
100
100
a See text for detailed procedures. Product was analyzed by H NMR.
b Conversion of 2a to 3a and 4a. c Molar ratio of 3a/4a. When product 4a
could not be detected by 1H NMR, a value of >99/1 was assigned. The
same applies to other tables. d Ratio of trans/cis isomers of 4a.
1
(27) For reviews, see: (a) Wilkes, J. S. J. Mol. Catal. A: Chem. 2004, 214, 11.
(b) Cole-Hamilton, D. J. Science 2003, 299, 1702. (c) Ionic Liquids as
Green SolVents; Rogers, R. D., Seddon, K. R., Eds.; ACS Symposium Series
856; American Chemical Society: Washington, DC, 2003. (d) Baudequin,
C.; Baudoux, J.; Levillain, J.; Cahard, D.; Gaumon, A.-C.; Plaquevent, J.-
C. Tetrahedron: Asymmetry 2003, 14, 3081. (e) Ionic Liquids in Synthesis;
Wasserscheid, P., Welton, T., Eds.; Wiley-VCH: Weinheim, Germany,
2003. (f) Dupont, J.; de Souza, R. F.; Suarez, P. A. Z. Chem. ReV. 2002,
102, 3367. (g) Olivier-Bourbigou, H.; Magna, L. J. Mol. Catal. A: Chem.
2002, 182-183, 419. (h) Zhao, D.; Wu, M.; Kou, Y.; Min, E. Catal. Today
2002, 74, 157. (i) Tzschucke, C. C.; Markert, C.; Bannwarth, M.; Roller,
S.; Hebel, A.; Haag, R. Angew. Chem., Int. Ed. 2002, 41, 3964. (j) Zhao,
H.; Malhotra, S. V. Aldrichimica Acta 2002, 35, 75. (k) Sheldon, R. Chem.
Commun. 2001, 2399. (l) Gordon, C. M. Appl. Catal., A 2001, 222, 101.
(m) Wasserscheid, P.; Keim, W. Angew. Chem., Int. Ed. 2000, 39, 3772.
(n) Welton, T. Chem. ReV. 1999, 99, 2071. (o) Seddon, K. R. J. Chem.
Technol. Biotechnol. 1997, 68, 351. (p) Chauvin, Y.; Olivier, H. CHEMTECH
1995, 25, 26. (q) Carlin, R. T.; Wilkes, J. S. In AdVances in Nonaqueous
Chemistry; Mamantov, G., Popov, A., Eds.; VCH: New York, 1994.
(28) For recent references reporting unusual catalytic activities and/or selectivities
in ionic liquids, see: (a) Earle, M. J.; McCormac, P. B.; Seddon, K. R.
Chem. Commun. 1998, 2245. (b) Song, C. E.; Shim, W. H.; Roh, E. J.;
Choi, J. H. Chem. Commun. 2000, 1695. (c) Song, C. E.; Shim, W. H.;
Roh, E. J.; Lee, S.; Choi, J. H. Chem. Commun. 2001, 1122. (d) Guernik,
S.; Wolfson, A.; Herskowitz, M.; Greenspoon, N.; Geresh, S. Chem.
Commun. 2001, 2314. (e) Boxwell, C. J.; Dyson, P. J.; Ellis, D. J.; Welton,
T. J. Am. Chem. Soc. 2002, 124, 9334. (f) Kim, D. W.; Song, C. E.; Chi,
D. Y. J. Am. Chem. Soc. 2002, 124, 10278. (g) Mehnert, C. P.; Dispenziere,
N. C.; Cook, R. A. Chem. Cmmun. 2002, 1610. (h) Bronger, R. P. J.; Silva,
S. M.; Kamer, P. C. J.; van Leeuwen, P. W. N. M. Chem. Commun. 2002,
3044. (i) Dupont, J.; Fonseca, G. S.; Umpierre, A. P.; Fichtner, P. F. P.;
Teixeira, S. R. J. Am. Chem. Soc. 2002, 124, 4228. (j) Oh, C. R.; Choo, D.
J.; Shim, W. H.; Lee, D. H.; Roh, E. J.; Lee, S.; Song, C. E. Chem. Commun.
2003, 1100. (k) Ngo, H. L.; Hu, A.; Lin, W. Chem. Commun. 2003, 1912.
(l) Fonseca, G. S.; Umpierre, A. P.; Fichtner, P. F. P.; Teixeira, S. R.;
Dupont, J. Chem.sEur. J. 2003, 9, 3263. (m) Kim, D. W.; Song, C. E.;
Chi, D. Y. J. Org. Chem. 2003, 68, 4281. (n) Shi, F.; Deng, Y.; SiMa, T.;
Peng, J.; Gu, Y.; Qiao, B. Angew. Chem., Int. Ed. 2003, 42, 3257. (o)
Chowdari, N. S.; Ramachary, D. B.; Barbas, C. F., III. Synlett 2003, 1906.
(p) Earle, M. J.; Katdare, S. P.; Seddon, K. R. Org. Lett. 2004, 6, 707. (q)
Doherty, S.; Goodrich, P.; Hardacre, C.; Luo, H. K.; Rooney, D. W.;
Seddon, K. R.; Styring, P. Green Chem. 2004, 6, 63.
to our delight, 1a was completely arylated by 2a in [bmim]-
[BF4] to give essentially exclusively the R-substituted product
3a; the 1H NMR spectrum of the reaction mixture after removing
the ionic liquid showed no sign of the linear olefin 4a,
suggesting that the ionic pathway B is operative in the ionic
liquid. In sharp contrast, with the six molecular solvents, some
of which are usually used in Heck reactions, none of the
reactions afforded a similar R/â ratio. DMSO produced the
highest R-regioselectivity among the molecular solvents, which
is consistent with its high polarity that is expected to promote
the ionic route.30 In the case of toluene, dioxane, and acetonitrile,
the reactions were also markedly slower. These results confirm
early observations, that is, mixtures of regioisomers result when
electron-rich olefins are arylated with aryl halides in molecular
solvents.7,8a,9c Little conversions (<1%) were observed in the
ionic liquids [bmim][X] (X ) Br or Cl), conceivably due to
halide coordination to palladium, which affects generation of
the cationic Pd-olefin species (vide infra), and/or the formation
of inactive 1-butyl-3-methylimidazol-2-ylidene complexes of
palladium.19f,31
The excellent regioselectivity observed in [bmim][BF4]
corroborates the arylation proceeding via the ionic pathway
made possible by the ionic medium. Although polar organic
solvents, such as DMSO and DMF, may facilitate halide
dissociation from palladium and the resulting high concentration
of Pd-olefin cations have been shown to give fast rates of olefin
insertion into Pd-Ar bonds,21,22 it is clear that none of the
molecular solvents alone are able to completely alter the reaction
pathway. However, as aforementioned, when water was intro-
duced into DMF, the resulting solvent mixture was capable of
(29) For recent references on Heck reactions in ionic liquids, see: (a) Calo`, V.;
Nacci, A.; Monopoli, A. J. Mol. Catal. A: Chem. 2004, 214, 45. (b) Calo,
V.; Nacci, A.; Monopoli, A.; Laera, S.; Cioffi, N. J. Org. Chem. 2003, 68,
2929. (c) Calo, V.; Nacci, A.; Monopoli, A.; Spinelli, M. Eur. J. Org. Chem.
2003, 1382. (d) Zou, G.; Wang, Z.; Zhu, J.; Tang, J.; He, M. Y. J. Mol.
Catal. A: Chem. 2003, 206, 193. (e) Choudary, B. M.; Madhi, S.; Chowdari,
N. S.; Kantam, M. L.; Sreedhar, B. J. Am. Chem. Soc. 2002, 124, 14127.
(f) Selvakumar, K.; Zapf, A.; Beller, M. Org. Lett. 2002, 4, 3031. (g) Okubo,
K.; Shiraib, M.; Yokoyama, C. Tetrahedron Lett. 2002, 43, 7115. (h)
Deshmukh, R. R.; Rajagopal, R.; Srinivasan, K. V. Chem. Commun. 2001,
1544. (i) Hagiwara, H.; Shimizu, Y.; Hoshi, T.; Suzuki, T.; Ando, M.;
Ohkubo, K.; Yokoyama, C. Tetrahedron Lett. 2001, 42, 4349. (j) Bohm,
V. P. W.; Herrmann, W. A. Chem.sEur. J. 2000, 6, 1017. (k) Carmichael,
A. J.; Earle, M. J.; Holbrey, J. D.; McCormac, P. B.; Seddon, K. R. Org.
Lett. 1999, 1, 997. (l) Ref 19d,f.
(30) The dielectric constants, which can be used as a quantitative measure of
solvent polarity, of the six molecular solvents range from 2.2 to 46.5.
(31) McLachlan, F.; Mathews, C. J.; Smith, P. J.; Welton, T. Organometallics
2003, 22, 5350. (b) Aggarwal, V. K.; Emme, I.; Mereu, A. Chem. Commun.
2002, 1612. (c) McGuinness, D. S.; Cavell, K. J.; Yates, B. F. Chem.
Commun. 2001, 355. (d) Mathews, C. J.; Smith, P. J.; Welton, T.; White,
A. J. P.; Williams, D. J. Organometallics 2001, 20, 3848. (e) Hasan, M.;
Kozhevnikov, I. V.; Siddiqui, M. R. H.; Femoni, C.; Stenier, A.; Winterton,
N. Inorg. Chem. 2001, 40, 795.
9
754 J. AM. CHEM. SOC. VOL. 127, NO. 2, 2005

Heck Arylation of Electron-Rich Olefins by Aryl Halides
A R T I C L E S
steric effects are minimal.13a The lack of reactivity with P(2-
toly)3 is probably due to the in situ formation of palladacycle
species, which normally require a higher temperature to activate
aryl bromides.4m,33 With DPPM, inactive binuclear palladium
species could be generated.34
Table 2. Ligand Effect on the Heck Arylation of Butyl Vinyl Ether
1a by 4-Bromobenzaldehyde 2a in [bmim][BF4]
Of particular note is that the activity and selectivity of the
palladium catalysts in the ionic liquid appear to correlate with
the bite angles of diphosphines.35 Full conversions were only
observed with ligands with relatively large bite angles (ca.
>90°), but high regiocontrol was only possible with ligands of
medium bite size. While bite angles affect both the oxidative
addition and olefin insertion steps, the latter appears to be more
likely here.36 Large bite angles could facilitate the dissociation
of halide ions from palladium due to steric repulsions, increasing
the concentration of Pd-olefin cations and presumably the
reaction rate as a result. van Leeuwen and co-workers have
recently reported that the cationic palladium species generated
from [L2Pd(Ph)Br] (L2 ) DPPE and XANTPHOS-type diphos-
phines) through bromide dissociation increases in concentration
when the ligand bite angle increases.37 Increasing the ligand
bite angle, which leads to increased steric interactions between
the inserting olefin and the phenyl rings at the phosphorus, could
also promote the R-selectivity by destabilizing the transition state
leading to the â-product.1c,13b However, when the bite angle
becomes too large, the ligand could inhibit rotation of the olefin
from out-of-plane coordination to an in-plane position necessary
for insertion, and if the rotation leading to the R-product is
severely affected and one of phosphorus atoms dissociates,5g,22,35d
reduced R-regioselectivities would result. In contrast, ligands
with smaller bite angles would be less inhibitive toward olefin
rotation, affording the R-product mainly under the influence of
electronic interactions. However, dissociation of the halide ion
or the insertion itself could be slow in this case, leading to lower
conversions. It thus appears that DPPP is the ligand of choice
for the least-resisting insertion pathway.
bite angle
(deg)b
conv.
(%)c
liganda
L/Pd
R
/
âc
E/Zc
none
PPh3
P(2-toly)3
DPPM
DPPE
DPPP
(R)-BINAP
DPPF
DPPB
XANTPHOS
4
66
2.0
2.0
1.1
1.1
1.1
1.1
1.1
1.1
1.0
76/24
75/25
<1
<1
17
100
100
100
100
100
72
85
91
92
96
>99/1
>99/1
93/7
50/50
45/55
31/69
89/11
75/25
79/21
72/28
98
112
a See Experimental Section for ligand nomenclature. b From ref 35b.
c Determined by H NMR.
1
promoting highly regioselective arylation by aryl bromides,
though not aryl iodides.25 Of further interest is the observation
that while decomposition of palladium complexes to various
degrees into palladium black always accompanied the arylation
in the molecular solvents, palladium black was rarely noticed
in the ionic liquid. Evidently, not only does [bmim][BF4]
promote the ionic pathway in the direct arylation of electron-
rich olefins by aryl halides to give preferentially the R-arylated
product but also it stabilizes the active palladium-phosphine
species in such reactions.
Effects of Ligands. As ligands are known to exert significant
effects on palladium-catalyzed Heck arylation reactions in
common organic solvents,1,3 we were interested in finding out
if ligands other than DPPP could also offer high regiocontrol
and high activity in the palladium-catalyzed arylation in the ionic
liquid [bmim][BF4]. The results on ligand screening, again using
4-bromobenzaldehyde 2a as the arylating agent, are given in
Table 2. It is clear that the choice of ligand is critical in
achieving good selectivities to the R-product alongside high
conversions, and as in the case of molecular solvents,9c the
combination of Pd(OAc)2 and DPPP affords the most selective
and active catalyst. Thus, with the catalyst so formed, the
arylation of 1a by 2a was complete within 24 h, leading to an
R/â product ratio of >99/1. In contrast, with all the other ligands
tested or in the absence of a phosphine, a lower selectivity and/
or a lower conversion were observed. BINAP is closest to DPPP
in terms of regioselectivity, affording an R/â ratio of 97/3.32
The regioselectivity with DPPP in [bmim][BF4] resembles that
observed with 1-naphthyl triflate in DMF, but the results with
DPPE, DPPB, and DPPF differ considerably in the two solvents,
with higher rates and/or higher R/â ratios being obtained in
DMF.9c The regioselectivity associated with PPh3 is consistent
with recent DFT calculations on a Pd(II)-L (L ) H2PCH2PH2
or PH3) model complex, which predict that vinyl ethers favor
R-arylation, regardless of the reaction pathway being ionic or
neutral, with the former being more R-selective, provided that
Comparative Arylation in [bmim][BF4] and DMF. En-
couraged by the results above, we first extended the arylation
reaction to the electrophiles 2b,c,e,x in [bmim][BF4]. To
determine if the ionic liquid would offer the same advantage
over common organic solvents for these substrates as well, the
same reaction experiments were performed in the most often
used solvent DMF. Table 3 summarizes the results obtained.
Clearly, in terms of regioselectivity, the ionic liquid is unsur-
passed. Thus, with each of the aryl bromides, compound 3 was
essentially the only product to be formed. By way of contrast,
the same reactions in DMF afforded mixtures of products, with
R/â ratios ranging from 46/54 to 69/31, which resemble the
results of 2a reacting with 1a in DMF and other common
solvents.
(33) Dupont, J.; Pfeffer, M.; Spencer, J. Eur. J. Inorg. Chem. 2001, 1917.
(34) Puddephatt, R. J. Chem. Soc. ReV. 1983, 12, 99.
(35) For reviews on bite angle effects in catalysis, see: (a) van Leeuwen, P. W.
N. M.; Kamer, P. C. J.; Reek, J. N. H.; Dierkes, P. Chem. ReV. 2000, 100,
2741. (b) Dierkes, P.; van Leeuwen, P. W. N. M. J. Chem. Soc., Dalton
Trans. 1999, 1519. (c) Casey, C. P.; Whiteker, G. T. Isr. J. Chem. 1990,
30, 299. For a study on the effect of diphosphines in amination of aryl
halides, see: (d) Hamann, B. C.; Hartwig, J. F. J. Am. Chem. Soc. 1998,
120, 3694.
(32) BINAP also displayed a high regioselectivity in R-vinylation of enamides
(36) The 14e species L2Pd(0) (Scheme 1, L2 ) diphosphine) is expected to be
more active in oxidative addition with L2 having a smaller bite angle: (a)
Otsuka, S. J. Organomet. Chem. 1980, 200, 191. (b) Hofmann, P.; Heiss,
H.; Mueller, G. Z. Naturforsch. 1987, B42, 395. (c) Ref 35b.
(37) Guari, Y.; van Strijdonck, G. P. F.; Boele, M. D. K.; Reek, J. N. H.; Kamer,
P. C. J.; van Leeuwen, P. W. N. M. Chem.sEur. J. 2001, 7, 475.
(ref 10a). For a reference comparing the reactivity of L2Pd(0) (L2
)
diphosphine, including BINAP) in oxidative addition, see: (a) Amatore,
C.; Broeker, G.; Jutand, A.; Khalil, F. J. Am. Chem. Soc. 1997, 119, 5176.
On a related study, see: (b) Alcazar-Roman, L. M.; Hartwig, J. F.
Organometallics 2002, 21, 491.
9
J. AM. CHEM. SOC. VOL. 127, NO. 2, 2005 755

A R T I C L E S
Mo et al.
Table 3. Heck Arylation of Butyl Vinyl Ether 1a by Aryl Halides 2
in [bmim][BF4] and DMF
Table 4. Heck Arylation of Butyl Vinyl Ether 1a by Aryl Bromides
2a-q in [bmim][BF4]a
T
time conv.b
(h) (%)
yieldd
(%)
ArXa
solvent
(
°
C)
R/
âc
E/Zc
p-CHOPh 2a
p-NCPh 2b
p-MeOCPh 2c [bmim][BF4] 120 24
[bmim][BF4] 100 24 100 >99/1
90
57
[bmim][BF4] 100 36
61 >99/1
21 >99/1
30 >99/1
45 >99/1
p-FPh 2e
[bmim][BF4] 100 24
25e
40
yieldc
(%)
yieldc
(%)
1-naph 2xf
[bmim][BF4]
DMF
80 36
R
productb
R
productb
2a
2b
2c
2e
2x
100 24 100 47/53 80/20 30
120 18 100 61/39 77/23 54
120 24 100 46/54 76/24 54
100 18 100 63/37 64/36 59e
80 24 100 69/31 66/34 54
DMF
DMF
DMF
DMF
p-CHO 2a
p-NC 2b
p-COMe 2c
p-CO2Me 2d
p-F 2e
5a
5b
5c
5d
5e
5f
5g
5h
5i
93
94
92
90
96
97
88
81
95
m-COMe 2j
m-CHO 2k
m-F 2l
m-Me 2m
m-MeO 2n
o-F 2o
5j
5k
5l
5m
5n
5o
5p
5q
87
83
81
80
86
81
86
95
a X) Br. b Conversion to 3 and 4; determined by 1H NMR. c Determined
by 1H NMR before acidification. d Isolated yield of 5 after acidification of
H 2f
p-Me 2g
p-MeO 2hd
m-NC 2i
o-OMe 2p
1
3. e Determined by H NMR and GC. f X ) I.
1-naph 2qe
Surprisingly, somehow for these aryl substrates, the reaction
became sluggish with the isolated yields for ketones 5 being
lower in comparison with that of 2a in [bmim][BF4]. Thus, the
arylation by 2b resulted in a conversion of only 61% in 36 h,
whereas with 2a, the reaction was complete within a reaction
time of 24 h. This is not the case with the reactions in DMF,
where full conversions were obtained with all of the bromides
under similar reaction conditions. The lower rates associated
with [bmim][BF4] result presumably from a decrease in the
quantity of the phosphine ligand as a consequence of its probable
involvement in the reduction of Pd(II) to Pd(0), with itself being
turned into a monophosphine ligand, DPPP monoxide [DPPP-
(O)].38 Palladium without a phosphine ligand or with a mono-
dentate phosphine displays a low activity in the arylation
reaction in [bmim][BF4] (Table 2), and the active catalyst
involved in the arylation is generally believed to be the 14e
species L2Pd(0) (Scheme 1).1 Consistent with this assumption,
replacement of Pd(OAc)2 by a Pd(0) complex, Pd2(dba)3 (dba
) dibenzylideneacetone), or more simply, addition of 1 equiv
more of DPPP led to a marked increase in the rate of arylation
in [bmim][BF4].39 For example, the conversion rose from 21 to
90% when Pd2(dba)3 was employed to replace Pd(OAc)2 in the
coupling of 4-bromoacetophenone 2c with 1a. The higher rates
and lower regioselectivities with DMF are indicative of both
neutral and ionic pathways being operative in this solvent, where
the active species may be Pd(0)-DPPP(O). We have previously
demonstrated that using 2 equiv of DPPP does not improve the
regioselectivities in DMF, and while 3 equiv of DPPP does,
the reaction is slow with a limited scope.40
a Reaction time of 24 h for 2a,c-g,q; 36 h for others. b All reactions
gave 100% conversion and >99/1 R/â selectivity as determined by 1H NMR
before acidification. c Isolated yield of 5. d With 4.0 mol % Pd(OAc)2 and
8.0 mol % DPPP. e 1-Bromonaphthalene.
summarized in Table 4. As can be seen, excellent regioselec-
tivities together with high isolated yields for the aryl methyl
ketones 5 were obtained in all of the reactions in the ionic liquid,
regardless of the nature of the substituents on the aryl rings.
Thus, bromobenzenes bearing either strongly electron-withdraw-
ing or electron-donating para substituents, such as -CN or
-OMe, all furnished good to excellent isolated yields, with R/â
ratios of >99/1. The same reaction can be equally applied to
meta-substituted bromobenzenes having either electron-with-
drawing or electron-donating groups, as demonstrated by the
substrates 2i-n. We were pleased that the protocol worked even
for some sterically hindered substrates, such as 2o-q, given
that a bulky bidentate ligand is bonded to the palladium center.
However, the sterically more demanding 2-bromo-1,3-dimeth-
ylbenzene furnished a conversion of only 9% in a 24 h reaction
time. The reactions proceeded smoothly in general, leading to
relatively clean products even without chromatographic purifica-
tion (see Supporting Information for an example). Under the
given conditions, all of the reactions shown in Table 4 went to
completion, but shorter times should be possible since the
reaction time was not optimized for each individual reaction
(vide infra). The remarkable regioselectivities observed with
[bmim][BF4] suggest that the neutral path A (Scheme 1) is either
completely suppressed or its involvement in the arylation in
the ionic liquid is insignificant. The protocol provides a
practically useful supplement to the known methodologies for
the synthesis of important aromatic ketones41 and particularly
to Friedel-Crafts acylation, which is neither effective toward
Arylation of Olefins 1a-h in [bmim][BF4]. On the basis
of the above studies, the arylation of 1a in [bmim][BF4] was
undertaken with a variety of aryl bromides in the presence of
Pd(OAc)2 and 2 equiv of DPPP. The results obtained are
(38) Amatore, C.; Jutand, A.; Thuilliez, A. Organometallics 2001, 20, 3241.
(b) Ozawa, F.; Kubo, A.; Hayashi, T. Chem. Lett. 1992, 2177. See also:
(c) Grushin, V. V. J. Am. Chem. Soc. 1999, 121, 5831 (for diphosphine
monoxides). Under amination conditions, oxidation of diphosphines does
not appear to occur, however: (d) Alcazar-Roman, L. M.; Hartwig, J. F.;
Rheingold, A. L.; Liable-Sands, L. M.; Guzei, I. A. J. Am. Chem. Soc.
2000, 122, 4618.
(41) Cacchi, S.; Fabrizi, G.; Gavazza, F.; Goggiamani, A. Org. Lett. 2003, 5,
289 and references therein. (b) Mizushima, E.; Sato, K.; Hayashi, T.;
Tanaka, M. Angew. Chem., Int. Ed. 2002, 41, 4563. (c) Duris, F.; Barbier-
Baudry, D.; Dormond, A.; Desmurs, J. R.; Bernard, J. M. J. Mol. Catal.
A: Chem. 2002, 188, 97. (d) Kaur, J.; Griffin, K.; Harrison, B.;
Kozhevnikov, I. V. J. Catal. 2002, 208, 448. (e) Frost, C. G.; Wadsworth,
K. J. Chem. Commun. 2001, 2316. (f) Walter, D. S. In ComprehensiVe
Organic Functional Group Transformations; Pattenden, G., Ed.; Perga-
mon: Oxford, 1995; Vol. 3, p 277.
(39) Addition of 2 equiv of DPPP to Pd(OAc)2 in DMF led to [Pd(DPPP)(OAc)]-
and DPPP(O), and with 3 equiv of DPPP, the inactive [Pd(0)(DPPP)2]
formed, according to ref 38a.
(40) Xu, L.; Chen, W.; Xiao, J. J. Mol. Catal. A: Chem. 2002, 187, 189.
9
756 J. AM. CHEM. SOC. VOL. 127, NO. 2, 2005

Heck Arylation of Electron-Rich Olefins by Aryl Halides
A R T I C L E S
Table 5. Heck Arylation of 1a by Aryl Iodides 2 in [bmim][BF4]
Table 6. Heck Arylation of Vinyl Ethers 1b-d with Aryl Halides 2
in [bmim][BF4]
yield
(%)b
producta
1b
1c
1d
R
producta
R
′
yield (%)b
p-CO2Me 2s
p-CHO 2t
H 2u
5c
5a
5f
5g
5h
5q
96
96
91
98
98
94
H 2f
p-F 2e
p-NC 2b
p-COMe 2c
p-CHO 2a
p-MeO 2hc
1-naph 2xd
5f
93
96
95
94
96
89
95
90
92
91
90
90
87
92
86
87
85
88
84
83
89
5e
5b
5c
5a
5h
5q
p-Me 2v
p-MeO 2w
1-naph 2xc
a All reactions gave 100% conversion and >99/1 R/â selectivity as
determined by 1H NMR before acidification of 3, which led to 5. b Isolated
yield of 5. c 1-Iodonaphthalene.
a All reactions gave 100% conversion and >99/1 R/â selectivity as
determined by 1H NMR before acidification of 3, which led to 5. b Isolated
yield of 5. c Reaction time of 36 h. d 1-Iodonaphthalene, 80 °C reaction
temperature.
electron-deficient arenes nor as regioselective as the current
method for the introduction of an acetyl group.42
Table 7. Heck Arylation of Enamides 1e-g by Aryl Bromides 2
Olefin 1a can also be arylated with aryl iodides. When going
from bromides to iodides, both electrostatic and hydrogen-
bonding interactions would be expected to become weaker,
which could render the ionic pathway less favorable as compared
with that in the case of bromides.23 This may explain why the
aforementioned DMF-H2O system failed with this class of
substrates.25 The arylation of 1a with aryl iodides in [bmim]-
[BF4] was carried out in the presence of Pd(OAc)2 and 2 equiv
of DPPP at 80 °C in a 24 h reaction time. As can be seen from
Table 5, the reactions of both electron-rich and electron-deficient
aryl iodides afforded, again, excellent regioselectivities and high
isolated yields for the ketones after acidic hydrolysis. Without
chelation assistance, regioselective arylation of electron-rich
olefins with aryl iodides and bromides is possible generally only
in the intramolecular version of the reaction, as aforementioned.
The vinyl ethers 1b-d have also proven to be viable
substrates. Examples of arylation with activated and deactivated
aryl bromides and an iodide are given in Table 6. All of the
reactions proceeded with >99/1 R/â-regioselectivities and
furnished aryl methyl ketones in yields of >80% after hydroly-
sis. The divinyl ether 1b was generally more effective, requiring
smaller amounts (0.75 equiv versus 5 equiv in the case of 1a,c,d)
and delivering better yields.
Enamides are another class of electron-rich olefins, and their
arylation could lead to synthetically and catalytically important
R-arylenamides.43 Somewhat surprisingly, there appears to be
no literature examples in which enamides are R-arylated with
aryl halides, although 1-naphthyl triflate and recently vinyl
triflates have been shown to react with enamides, regioselec-
tively furnishing branched olefins.9a,10a More recently, Larhed
and co-workers have reported successful regioselective coupling
of 1e-g with arylboronic acids in 1,4-dioxane, using a phenan-
throline ligand for palladium under an atmosphere of oxygen.17
Applying the conditions established for the vinyl ethers, we were
disappointed to find that enamides 1e and 1f showed little sign
of coupling with the bromoacetophenone 2c in [bmim][BF4].
yield
(%)b
aryl bromides
enamides
productsa
2c
2e
2f
2o
2rc
2c
2e
2g
2r
2f
1e
1e
1e
1e
1e
1f
1f
1f
1f
1g
1g
3ec
3ee
3ef
3eo
3er
3fc
3fe
3fg
3fr
3gf
3gr
85
80
82
74
86
83
85
73
78
76
71
2r
a Full conversions and >99/1 R/â selectivity for all as determined by
1H NMR. b Isolated yield. c 2-Bromonaphthalene.
Unexpectedly, when DMSO was introduced as cosolvent,
smooth, regioselective arylation of 1e-g took place. Table 7
summarizes the results obtained with Pd-DPPP in a 1:1
(volume) mixture of [bmim][BF4] and DMSO. It must be
pointed out that in neat DMSO, a mixture of species was formed
in which the only olefinic product, 3, was insignificant. In
comparison with Larhed’s oxidative coupling using the more
costly arylboronic acids,17 the reactions of Table 7 required
harsher conditions but afforded in general higher regioselec-
tivities (>99/1 versus 92/8-99/1) and higher yields (71-86%
versus 31-96%). With both methods, aryl substrates bearing
the strongly electron-withdrawing -CN group failed to give
good conversions, however. The role of DMSO is not entirely
clear to us; it may facilitate â-hydrogen elimination by replacing
the coordinated amine from palladium. Amine coordination
could occur following aryl insertion, impeding the access of
â-hydrogen to palladium.44
(42) Olah, G. A.; Krishnamurti, R.; Prakash, G. K. S. In ComprehensiVe Organic
Synthesis; Trost, B. M., Ed.; Pergamon: Oxford, 1991; Vol. 3, p 293. (b)
Heaney, H. In ComprehensiVe Organic Synthesis; Trost, B. M., Ed.;
Pergamon: Oxford, 1991; Vol. 2, p 733.
(43) Burk, M. J.; Wang, Y. M.; Lee, J. R. J. Am. Chem. Soc. 1996, 118, 5142
and references therein.
(44) Hegedus, L. S. Transition Metals in the Synthesis of Complex Organic
Molecules, 2nd ed.; University Science Books: Sausalito, CA, 1999;
Chapter 7.2. DMSO was also found to improve regioselectivities of the
arylation of unfunctionalized cycloalkenes by aryl bromides: (b) Hartung,
C. G.; Ko¨hler, K.; Beller, M. Org. Lett. 1999, 1, 709.
9
J. AM. CHEM. SOC. VOL. 127, NO. 2, 2005 757

A R T I C L E S
Mo et al.
Table 8. Heck Arylation of Allyltrimethylsilane 1h by Aryl Halides
2a-g in [bmim][BF4]
Table 9. Effect of Bromide Ion on the Heck Arylation of 1a by 2c
in [bmim][BF4]
Conv. (%)a
nBu4NBr
(mmol)
conv.
(%)b
yield
(%)c
Pd(OAc)2/nBu4NBr
6 h
12 h
substrate
producta
59
32
20
6
4
3
96
63
48
12
5
2a
2b
2c
2d
2e
2f
3ha
3hb
3hc
3hd
3he
3hf
92
81
100
91
100
100
96
82
65
93
85
89
88
89
0.025
0.05
0.13
0.25b
0.50
1:1
1:2
1:5
1:10
1:20
3
2g
3hg
a Determined by 1H NMR after acidification of 3c at the time indicated;
average of three runs. b Employing the same quantity of nBu4NCl afforded
similar conversions: 5% (6 h) and 7% (12 h).
a All reactions gave >99/1 â/γ selectivity as determined by H NMR.
1
b Determined by H NMR. c Isolated yield.
1
Mechanistic Observations. As aforementioned, it is gener-
ally agreed that the Heck reaction proceeds via a neutral and/or
an ionic pathway, and when the latter is in operation, electron-
rich olefins lead in general to R-arylation.1,9-11,13 Except for
intramolecular arylation reactions, where aryl iodides can be
employed and coordination of the olefin may assist the
dissociation of the iodide generating a palladium-olefin cation
(Scheme 1),6 the vast majority of the Heck arylation reactions
that follow the ionic mechanism rely on aryl triflates as
substrates. In fact, Brown has shown that the complex [L2Pd-
(Ar)I] (L2 ) DPPF), in which the Ar group bears an ortho-
vinyl ether substituent, is thermally stable in THF and undergoes
intramolecular cyclization (at -40 °C in d6-acetone) only when
the iodide is removed with AgOTf.49 The results we obtained
with aryl bromides and iodides, without using any halide
scavenger, are consistent with those of the arylation proceeding
via the ionic pathway, with dissociation of the halide anion from
palladium promoted by the ionic liquid. More direct supporting
evidence comes from reactions in the presence of added halide
anions. Thus, as shown in Table 9, the arylation of 1a by 2c
was notably slowed even when 1 equiv of Br- (relative to
To further explore the scope of this highly regioselective Heck
arylation method, the arylation of allyltrimethylsilane 1h was
examined. The arylated branched allylsilanes are important
intermediates in organic synthesis, including palladium-catalyzed
C-C bond formation.45 Unfortunately, under traditional Heck
reaction conditions, arylation of allyltrimethylsilane with aryl
halides affords linear arylated silanes, even in the presence of
silver additives.46,47 In contrast, when performed in the ionic
environment provided by [bmim][BF4], arylation with aryl
bromides of diverse electronic properties proceeded regiose-
lectively to give branched allylsilanes in good to excellent yields.
Thus, the aryl bromides 2a-g reacted with allyltrimethylsilane
1h, furnishing exclusively the â-arylated allylsilanes in 65-
93% isolated yields in the presence of Pd(OAc)2 and DPPP in
[bmim][BF4] (Table 8). Similar regioselective arylation of
allyltrimethylsilane could also be achieved in CH3CN, but aryl
triflates were necessary, according to Hallberg and co-
workers.10g In addition to relying on triflates, the yields (31-
85%) were generally lower in comparison with those of the ionic
liquid protocol described here, however. Hallberg has suggested
that the reaction proceeds via the ionic pathway, with the key
step being migration of the aryl group to the positively charged
carbon â to and stabilized by the SiMe3 unit [which could be
understood as arising from the olefin acting as a Lewis base
attacking the electrophilic palladium(II)]. The excellent â-se-
lectivities we observed in the ionic liquid are in line with this
view. DMSO was not required in this case, however, probably
because product inhibition via chelation is unlikely. Owing to
its superior selectivity and yield and functional group compat-
ibility, the present method compares favorably with available
methods in the literature for the preparation of â-arylated
allylsilanes.48
n
palladium, in the form of Bu4NBr) was introduced into the
solvent [bmim][BF4], and the reaction rate was progressively
n
reduced when more Bu4NBr was added. A similar effect was
also observed with nBu4NCl. This is consistent with there being
an equilibrium, as shown in eq 2, which is shifted toward the
left on addition of the halide ions, reducing the concentration
of cationic Pd-olefin species and consequently the reaction
rate.50 Similar observations have been made in arylation
reactions using aryl triflates5g,9c and in the stoichiometric reaction
of [L2Pd(Ar)Cl] (L2 ) diphosphine) with olefins,22 using
molecular solvents in both cases, and these have been taken as
evidence in support of the ionic mechanism.
(45) Barbero, A.; Castren˜o, P.; Pulido, F. J. Org. Lett. 2003, 5, 4045. (b) Furman,
B.; Dziedzic, M. Tetrahedron Lett. 2003, 44, 8249. (c) Furman, B.;
Dziedzic, M. Tetrahedron Lett. 2003, 44, 6629. (d) Kuroda, C.; Kasahara,
T.; Akiyama, K.; Amemiya, T.; Kunishima, T.; Kimura, Y. Tetrahedron
2002, 58, 4493. (e) Mendez, M.; Echavarren, A. M. Eur. J. Org. Chem.
2002, 15. (f) Friestad, G. K.; Ding, H. Angew. Chem., Int. Ed. 2001, 40,
4491. (g) Ofial, A. R.; Mayr, H. J. Org. Chem. 1996, 61, 5823. (h) Takeda,
T.; Takagi, Y.; Takano, H.; Fujiwara, T. Tetrahedron Lett. 1992, 33, 5381.
(i) Pernez, S.; Hamelin, J. Tetrahedron Lett. 1989, 26, 3419.
(46) Karabelas, K.; Westerlund, C.; Hallberg, A. J. Org. Chem. 1985, 50, 3896.
(47) For an example of regiolselective intramolecular vinylation of allylsilane
with vinyl triflates and iodides, see: Tietze, L. F.; Modi, A. Eur. J. Org.
Chem. 2000, 1959.
(48) Monfray, J.; Gelas-Mialhe, Y.; Gramain, J.-C.; Remuson, R. Tetrahedron
Lett. 2003, 44, 5785. (b) Ref 10g and references therein.
If the assertion above is true, it must mean that the HBr
generated in the last step of the Heck cycle (Scheme 1) is
(49) Brown, J. M.; Pe´rez-Torrente, J. J.; Alcock, N. W.; Clase, H. J. Organo-
metallics 1995, 14, 207.
(50) The oxidation addition step may well benefit from the added anions: (a)
Roy, A. H.; Hartwig, J. F. Organometallics 2004, 23, 194. (b) Ref 38a.
9
758 J. AM. CHEM. SOC. VOL. 127, NO. 2, 2005

Heck Arylation of Electron-Rich Olefins by Aryl Halides
A R T I C L E S
Table 10. Effect of Ionic Liquid Cation on the Arylation of 1a by
2a
yield after hydrolysis of 3c (eq 4). This result can be viewed as
resulting from preferential bonding of an electron-deficient Pd-
(II) cation with an electron-rich olefin. By way of contrast, in
DMF, the opposite chemoselectivity was observed when
1-naphthyl iodide was reacted with a mixture of 1a and methyl
acrylate, due to preferential coordination of the electron-poor
methyl acrylate to an electron-rich, neutral Pd(II) center.
Preferential reaction of the vinyl ether 1a was observed only
when the naphthyl iodide was replaced with the corresponding
triflate.9b
a Determined by NMR at the time indicated; >99/1 R/â ratios; average
of two runs.
effectively scavenged by NEt3 in the ionic liquid. It also means
that the aforesaid hydrogen bond contribution to the dissociation
of Br- from palladium is insignificant, if any. Indeed, the
arylation of 1a by 2a proceeded even slightly faster in 1-butyl-
2,3-dimethylimidazolium tetrafluoroborate ([bdmim][BF4]), in
which the H2 ring proton was replaced with a methyl group
(Table 10). The H2 proton is the most acidic among the three
imidazolium ring protons and usually forms the strongest
hydrogen bonds with anions.23
Conclusions
The past several years have witnessed great strides in
developing active and productive catalysts for the Heck reac-
tion.1,2 These catalysts in general do not lead to regioselective
reactions in intermolecular arylation of electron-rich olefins with
aryl halides, however. For these olefins, the arylation is most
frequently carried out by employing commercially inaccessible
aryl triflates, and when aryl halides are chosen, stoichiometrical
silver or thallium salts are generally needed. This paper
demonstrates that imidazolium ionic liquids in combination with
the readily available Pd(OAc)2 and DPPP form an excellent
catalytic system, with which highly regioselective and yielding
arylation of several classes of electron-rich olefins can be
accomplished with a wide range of aryl halides with no need
for any halide scavengers. Specifically, we demonstrated that
vinyl ethers, enamides, and allyltrimethylsilane can be arylated
under Pd-DPPP catalysis by various aryl bromides and iodides
in the ionic liquid [bmim][BF4] or in [bmim][BF4]-DMSO in
the case of the enamides, with all of the reactions furnishing
essentially only the branched olefins in high isolated yields. The
chemistry thus provides a viable synthetic pathway to R-arylated
vinyl ethers and enamides, aryl ketones, and â-arylated allylic
silanes that are of value to synthetic chemistry. While the
detailed reaction mechanism remains to be delineated, our results
suggest that the reaction proceeds via the ionic pathway, hence,
giving rise to the branched product. The ionic liquid plays a
pivotal role in making this possible, presumably by facilitating
the dissociation of halide anions from palladium. Given the
designer properties of ionic liquids,27 improvements on the
current method in terms of reaction rates and catalyst loadings
and solutions to other difficult substrates for the Heck and related
reactions are foreseeable.28
So how were the bromide anions removed during the arylation
reactions? No precipitated salt was visible in any of the reactions
in [bmim][BF4], and the salt [HNEt3][Br] (prepared from NEt3
and HBr) is actually quite soluble in this ionic liquid (>1.5
M); hence, the bromide ions were not removed by precipita-
tion.51 While we have no clear answer to the question, one
possible explanation might be that the bromide ions form tight
ion pairs with protonated NEt3, [H-NEt3]+, via hydrogen
bonding. In line with this, introduction of additional hydrogen
-
bond donor [H-NEt3]+ (in the form of its BF4 salt) into the
reaction of 1a with 2 resulted in significantly faster rates, as
shown by the examples given in eq 3, using both electron-
deficient and -rich aryl bromides. Thus, for instance, the
arylation of 1a by 2c gave a full conversion in 6 h when 10
equiv (relative to the catalyst) of [HNEt3][BF4] was added; in
its absence, the conversion was 96% in 12 h (Table 9). These
results are remarkable, as they resemble those obtained by using
stoichiometric Tl(OAc) in the arylation of 1a by 2c under similar
conditions, which led to a full conversion within 6 h (R/â >99/
1) by forming insoluble TlBr.
A further demonstration of the ionic Heck pathway operating
in the ionic liquid is seen in the competition reaction of butyl
vinyl ether 1a, styrene, and methyl acrylate with 4′-bromoac-
etophenone 2c. Of the three olefins, only the electron-rich 1a
reacted in [bmim][BF4], affording ketone 5c in 88% isolated
(51) One possibility is the formation of [bmim][Br] as tight ion pairs, but if
this were the case, the added Br- would be equally removed by the solvent
cations. For discussions on ion pairs in ionic liquids, see: (a) Fry, A. J. J.
Electroanal. Chem. 2003, 546, 35. (b) Jensen, M. P.; Neuefeind, J.; Beitz,
J. V.; Skanthakumar, S.; Soderholm, L. J. Am. Chem. Soc. 2003, 125, 15466.
(c) Lancaster, N. L.; Salter, P. A.; Welton, T.; Young, G. B. J. Org. Chem.
2002, 67, 8855. (d) Gannon, T. J.; Law, G.; Watson, P. R.; Carmichael, A.
J.; Seddon, K. R. Langmuir 1999, 15, 8429.
Experimental Section
All reactions were carried out under a nitrogen atmosphere.
Chromatographic purifications were performed on silica gel (mesh
9
J. AM. CHEM. SOC. VOL. 127, NO. 2, 2005 759

A R T I C L E S
Mo et al.
230-400) by the flash technique. 1-Butyl-3-methylimidazolium tet-
rafluoroborate ([bmim][BF4]) was prepared according to the literature
method.52 After vacuum-drying at 80 °C for 8 h, the ionic liquid was
stored under nitrogen at ambient temperature, and prior to use, it was
vacuum-dried again at 80 °C for 1 h. However, our more recent
experiments have shown that water (up to 10 wt %) does not have an
adverse effect on the arylation of this study. AgNO3 titration showed
the chloride content of the ionic liquid to be below detection limit
(<0.2%). Vinyl ethers 1a-d, enamides 1e-g, allyltrimethylsilane 1h,
aryl halides 2a-x, Pd(OAc)2, 1,2-bis(diphenylphosphino)methane
(DPPM), 1,2-bis(diphenylphosphino)ethane (DPPE), 1,3-bis(diphe-
nylphosphino)propane (DPPP), 1,4-bis(diphenylphosphino)butane (DPPB),
1,1-bis(diphenylphosphino)ferrocene (DPPF), (R)-2,2′-bis(diphenylphos-
phino)-1,1′-binaphthyl [(R)-BINAP], 4,5-bis(diphenylphosphino)-9,9-
dimethylxanthene (XANTPHOS), and triethylamine were purchased
nitrogen at room temperature. After the mixture was degassed three
times, vinyl ether 1 (5.0 mmol) and NEt3 (1.2 mmol) were injected
sequentially. The flask was placed in an oil bath, and the mixture was
stirred and heated at the desired temperature. After an appropriate
reaction time, the flask was removed from the oil bath and cooled to
room temperature. A small sample was then taken for NMR analysis.
In all of the reactions, the â-arylated product was not detected. To the
rest of the mixture was added aqueous HCl (5%, 5 mL), and after the
mixture was stirred for 0.5 h, CH2Cl2 (20 mL) was added. After
separation of the CH2Cl2 phase, the aqueous layer was extracted with
CH2Cl2 (2 × 20 mL), and the combined organic layer was washed
with water (until neutral), dried (Na2SO4), filtered, and concentrated
in vacuo. The aryl methyl ketone 5 was isolated out of the crude product
by flash chromatography on silica gel using a mixture of ethyl acetate
and hexane (1/99-10/90) as eluant. The identity and purity of the
product were confirmed by 1H and 13C NMR, MS, HRMS, and
elemental analysis and by comparison of their NMR spectra with
available literature data. The isolated yields of the products are given
in Tables 4-6. Similar procedures were adopted for the arylation in
molecular solvents.
1
from Lancaster and Aldrich and were used as received. H and 13C
NMR spectra were recorded on a Gemini 400 spectrometer at 400 (1H)
and 100 MHz (13C) in parts per million with reference to TMS internal
standard in CDCl3. Mass spectra were obtained by chemical ionization
1
(CI). All of the products were satisfactorily characterized by H and
13C NMR, MS, HRMS, and/or elemental analysis, and when possible,
comparison of their NMR spectra has been made with available
literature data and/or those of authentic samples. The following
compounds have all been reported previously: (E/Z)-4-(2-butoxyethe-
nyl)benzaldehyde 4a,4g (E/Z)-4-(2-butoxyethenyl)benzonitrile 4b [127087-
66-5],9e (E/Z)-1-butoxy-2-(4-acetylphenyl)ethylene 4c,9a (E/Z)-1-(2-
butoxyethenyl)naphthalene 4q [127087-65-4],9e ketones 5a [3457-45-
2],53 5b [1443-80-7],54 5c [1009-61-6],54 5d [3609-53-8],54 5e [403-
42-9],54 5f [98-86-2],54 5g [122-00-9],54 5h [100-06-1],54 5i [6136-68-
1],54 5j [586-37-8],54 5k [41908-11-6],55 5l [455-36-7],54 5m [585-74-
0],54 5n [586-37-8],54 5o [445-27-2],54 5p [4079-52-1],54 and 5q [941-
98-0],54 4-(1-trimethylsilanylmethylvinyl)benzaldehyde (3ha) [137190-
14-8],56 4-(1-trimethylsilanylmethylvinyl)benzonitrile (3hb),10g 1-[4-
(1-trimethylsilanylmethylvinyl)phenyl]ethanone (3hc),10g [2-(4-fluo-
rophenyl)allyl]trimethylsilane (3he) [139214-37-2],57 (2-phenylallyl)-
trimethylsilane (3hf) [77130-15-5],58 and trimethyl-(2-p-tolylallyl)silane
(3hg) [139214-35-0].58
General Procedure for the Heck Arylation of Enamides in Ionic
Liquid-DMSO. An oven-dried, two-necked round-bottom flask
containing a stir bar was charged with an aryl bromide 2 (1.0 mmol),
enamide 1 (1.0 mmol), Pd(OAc)2 (0.04 mmol), DPPP (0.08 mmol),
DMSO (1 mL), and [bmim][BF4] (1 mL) under nitrogen at room
temperature. After the mixture was degassed three times, NEt3 (1.2
mmol) was injected. The flask was placed in an oil bath, and the mixture
was stirred and heated at 115 °C. After a reaction time of 36 h, the
flask was removed from the oil bath and cooled to room temperature
for workup using a procedure similar to that given above. The isolated
yields of the products are given in Table 7.
General Procedure for the Heck Arylation of Allyltrimethylsilane
in Ionic Liquid. An oven-dried, two-necked round-bottom flask
containing a stir bar was charged with an aryl bromide 2 (1.0 mmol),
Pd(OAc)2 (0.04 mmol), DPPP (0.08 mmol), and [bmim][BF4] (2 mL)
under nitrogen at room temperature. After the mixture was degassed
three times, allyltrimethylsilane 1h (4.0 mmol) and NEt3 (1.2 mmol)
were injected sequentially. The flask was placed in an oil bath, and
the mixture was stirred and heated at 115 °C. After a reaction time of
36 h, the flask was removed from the oil bath and cooled to room
temperature for workup using a procedure similar to that given above.
The isolated yields of the products are given in Table 8.
General Procedure for the Heck Arylation of Vinyl Ethers in
Ionic Liquid. An oven-dried, two-necked round-bottom flask containing
a stir bar was charged with an aryl halide 2 (1.0 mmol), Pd(OAc)2
(0.025 mmol), DPPP (0.05 mmol), and [bmim][BF4] (2 mL) under
(52) Holbrey, J. D.; Seddon, K. R. J. Chem. Soc., Dalton Trans. 1999, 2133.
(53) Ichinose, N.; Mizuno, K.; Otsuji, Y.; Caldwell, R.; Helms, A. M. J. Org.
Chem. 1998, 63, 3176.
(54) Buckingham, J. Dictionary of Organic Compounds, 5th ed.; Chapman
Hall: New York, 1982. (b) Pouchert, C. J. The Aldrich Library of Infrared
Spectra, 3rd ed.; Aldrich Chemical Co.: Milwaukee, WI, 1981. (c) Pouchert,
C. J. The Aldrich Library of NMR Spectra, 2nd ed.; Aldrich Chemical
Co.: Milwaukee, WI, 1983.
(55) Bromilow, J.; Brownlee, R. T. C.; Craik, D. J.; Fiske, P. R.; Rowe, J. E.;
Sadek, M. J. Chem. Soc., Perkin Trans. 2 1981, 753.
(56) Kang, K.-T.; Kim, S. S.; Lee, J. C. Tetrahedron Lett. 1991, 32, 4341.
(57) O’Neill, P. M.; Pugh, M.; Stachuski, A. V.; Ward, S. A.; Davies, J.; Park,
B. K. J. Chem. Soc., Perkin Trans. 1 2001, 2682.
(58) Wong, K.-T.; Ni, Z.-J.; Luh, T.-Y. J. Chem. Soc., Perkin Trans. 1 1991,
3113.
Acknowledgment. We thank Synetix for support, and Dr.
Lixin Zhang for assistance. We are also grateful to Johnson
Matthey for the loan of palladium.
Supporting Information Available: Experimental procedures
for the arylation reactions, analytic data for all the products,
and sample 1H NMR spectra. This material is available free of
charge via the Internet at http://pubs.acs.org.
JA0450861
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760 J. AM. CHEM. SOC. VOL. 127, NO. 2, 2005